Adjuvant Treatment For Patients Research Articles

Does Adjuvant Gamma Knife Stereotactic Radiosurgery Have a Role in Treating Optic Nerve Sheath Meningiomas?

Meningiomas arising from or adjacent to the optic nerve sheath meningioma (ONSM) are management challenges because of their risk of visual loss. Stereotactic radiosurgery (SRS) is a minimally invasive modality that can be added as adjuvant treatment for patients whose tumor has progressed or recurred after initial resection. The authors retrospectively reviewed 2,030 meningioma patients who underwent SRS between 1987 and 2022. In total, 7 patients (4 females; median age = 49) were found with tumors originating from the optic nerve sheath. None of the patients had tumors that engulfed the optic nerve as such tumors typically undergo fractionated radiation therapy (FRT) to preserve vision. The clinical history, visual function, and radiographic and neurological findings were characterized. Outcome measures included visual status, tumor control, and the need for additional management. All patients underwent either initial gross total (n = 1) or partial surgical resection (n = 6) before SRS. Two patients with progressive tumor growth also had SRS after failing additional fractionated radiation after surgery (54 Gy, 30 fractions for both patients). The median time between the date of surgery and the SRS procedure date was 38 months. The Leksell Gamma Knife was used to deliver a margin dose of 12 Gy (range: 8-14 Gy) to a median cumulative tumor volume of 3.3 cc (range: 1.2-18 cc). The median maximal optic nerve radiation dose was 6.5 Gy (range: 1.9-8.1 Gy). After SRS, the median follow-up time was 130 months (range: 26-169 months). Two patients showed local tumor progression at 20 and 55 months after SRS. Four had stable visual function, 2 experienced improved visual acuity, and 1 patient had visual deterioration. Meningiomas arising from (but not engulfing the optic nerve) represent management quandaries after failed initial surgical removal. In this experience, salvage SRS was associated with tumor control and vision preservation in 5 of 7 patients. Additional experience with this strategy may further define the role of SRS both as a salvage and primary option.

A comprehensive correlation of the KI-67 proliferation index to patient´s, imaging and tumor features and its value in predicting long-term course of patients with newly diagnosed intracranial meningiomas.

To analyze the correlation of KI-67-Proliferation Index (KI-67-PI) with preoperative patients and MRI characteristics, WHO grading, histological subtype and long-term-course of patients with newly diagnosed intracranial meningiomas (IM). In this single-center retrospective study, all consecutive patients with IM were analyzed from January 2007 to August 2019. Patient´s demographics (age, sex), imaging parameters (location, volume, edema, necrosis), and tumor features (WHO grade, histology) were assessed and correlated with KI-67-PI. Long-term data were retrieved from patient's last follow-up visits. This study included 463 IM in 457 surgically treated patients. Males exhibited a higher KI-67-PI than females (7.31 ± 0.22 vs. 5.37 ± 0.53; p < 0.01, Mann-Whitney U Test). Age positively correlated with KI-67-PI in both sexes (p < 0.01, Spearman), with older patients having a higher KI-67-PI. KI-67-PI was significantly higher in convexity IM compared to frontobasal IM (7.15 ± 5.56 vs. 4.66 ± 2.94; p < 0.05, ANOVA, Tukey´s HSD), while no difference in KI-67-PI expression was found when other locations were compared to each other (Tukey´s HSD). Higher KI-67-PI was significantly correlated with larger tumor volume (p < 0.01, Spearman), larger tumor necrosis and larger peritumoral edema (p < 0.01, Kruskal-Wallis). Patients with recurrent IM had a significantly higher KI-67-PI than patients without recurrence (8.24 ± 5.88 vs. 5.14 ± 3.53; p < 0.01, ANOVA, Tukey´s HSD) during a mean follow-up period of 80.92 ± 38.1months. Atypical and anaplastic IM exhibited significantly higher KI-67-PI compared to all other WHO grade 1 histological subtypes (12.09 ± 0.73 vs. 4.51 ± 0.13; p < 0.01, Kruskal-Wallis test) and KI-67-PI was significantly higher in anaplastic IM compared to atypical meningioma (19.67 ± 1.41 vs. 11.01 ± 0.38; p < 0.01, ANOVA). Higher KI-67-PI is not only associated with atypical and anaplastic subtypes of IM, but is also significantly higher in males, positively correlates with patients age, larger tumor volume, lager peritumoral edema and necrosis on preoperative MRI and predicts tumor recurrence. Therefore, KI-67-PI may serve as a decision indicator for adjuvant treatment in patients with IM.

Prophylactic use of standardized extract of propolis of Apis mellifera (EPP-AF®) reduces lung inflammation and improves survival in experimental lethal sepsis

Ethnopharmacological relevanceSepsis poses one of the biggest public health problems, necessitating the search for new therapeutic alternatives. For centuries, propolis has been widely used in folk medicine to treat various inflammatory and infectious diseases. Given its extensive use, it has excellent potential as an adjuvant treatment for patients with sepsis. ObjectiveThis study evaluated prophylactic treatment with standardized propolis extract (EPP-AF®) and followed the prognosis of sepsis induced by ligation and cecal ligation and puncture (CLP). MethodsInitially, for survival assessment, Swiss mice were separated into five groups: Sham (false operated), control (PBS), ATB (received antibiotic, 8 mg/kg), P10 (received EPP-AF®, 10 mg/kg), and P100 (received EPP-AF®, 100 mg/kg). The animals received PBS, antibiotic, or EPP-AF® by the subcutaneous route 6 h before the CLP procedure. Animal survival was assessed every 12 h for five days when all of them were euthanized. ResultsWe show that the treatment with EPP-AF® significantly increased the life expectancy of animals with sepsis compared to the control group. Interestingly, prophylactic treatment with EPP-AF® showed no effect on the number of colony-forming units in the peritoneum, blood, or lung. However, there was a decrease in cellular influx in the peritoneum. This alteration was unrelated to the number of bone marrow cells or the differential counting of peripheral blood cells. The coagulogram remained unchanged, including the number of platelets and prothrombin time-activated partial thromboplastin time. However, the inflammatory infiltrate and bleeding in the lung tissue were lower in the animals that received EPP-AF®. ConclusionThus, it was possible to conclude that prophylactic treatment with EPP-AF® preserved the lung parenchyma, resulting in an increased lifespan of mice with sepsis. It can be a helpful adjuvant in prophylactic treatment with antibiotics in presurgical conditions.

Abstract GS03-03: Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2− early breast cancer: final invasive disease–free survival (iDFS) analysis from the NATALEE trial

Abstract Background: Interim results from the phase 3 NATALEE trial demonstrated that adding RIB to standard-of-care adjuvant NSAI had a statistically significant iDFS benefit in patients with stage II and III HR+/HER2− early breast cancer at risk of recurrence, including those with node-negative disease (Slamon et al, ASCO 2023). We present the final protocol-specified analysis of the primary endpoint of iDFS. Methods: A total of 5101 pre-/postmenopausal women and men underwent 1:1 randomization to receive RIB (400 mg/day; 3 weeks on/1 week off for 36 months) + NSAI (letrozole 2.5 mg/day or anastrozole 1 mg/day for ≥60 months) or NSAI alone. Men and premenopausal women received goserelin (3.6 mg once every 28 days). Patients were required to have anatomic stage IIA (either N0 with additional risk factors or N1), IIB, or III breast cancer per the AJCC (8th edition). Patients remained on trial as long as they were continuing on NSAI (≤5 years), regardless of RIB discontinuation. The primary endpoint was iDFS according to STEEP v1.0 criteria, and the secondary efficacy endpoints were recurrence-free survival (RFS), distant disease–free survival (DDFS), and overall survival (OS). This final analysis was planned after approximately 500 iDFS events. iDFS was evaluated by the Kaplan-Meier method, and statistical comparison was made by a stratified log-rank test. P values were not corrected for multiple comparisons. Results: At the data cutoff (July 21, 2023), among the 2549 patients in the RIB + NSAI arm, 1091 (42.8%) completed 3 years of RIB treatment, and 905 (35.5%) discontinued RIB or RIB + NSAI early and 528 patients (20.7%) remained on RIB. 1748 patients (68.5%) remain on treatment in the NSAI arm. Median follow-up for iDFS was 33.3 months, an additional 5.6 months from the previous interim analysis. A total of 509 iDFS events were observed, 226 (8.9%) in the RIB + NSAI arm and 283 (11.1%) in the NSAI alone arm. RIB + NSAI demonstrated a significant iDFS benefit over NSAI alone (HR, 0.749; 95% CI, 0.628-0.892; P=.0006). The 3-year iDFS rates were 90.7% (95% CI, 89.3%-91.8%) vs 87.6% (95% CI, 86.1%-88.9%). A consistent benefit was observed across patient subgroups, including those with node-negative, stage II, or stage III disease (Table). Secondary endpoints of DDFS and RFS favored RIB + NSAI over NSAI alone (Table). OS data were immature, with 84 (3.3%) and 88 (3.4%) total events in the RIB + NSAI and NSAI alone arms, respectively. No new safety signals were observed since the prior interim analysis. Discontinuation of RIB due to adverse events was observed in 19.5% of patients (a &amp;lt;1% increase from the prior interim analysis). Conclusions: With a substantial proportion of patients completing 3 years of RIB treatment, NATALEE continues to demonstrate a significant iDFS improvement with RIB + NSAI over NSAI alone. Efficacy results confirm continued improvement in benefit across subgroups, including stage II disease. Safety findings support the manageable toxicity profile of RIB at the 400-mg starting dose in early breast cancer. Table. Citation Format: Gabriel Hortobagyi, Daniil Stroyakovsky, Denise Yardley, Chiun-Shen Huang, Peter A. Fasching, John Crown, Aditya Bardia, Stephen Chia, Seock-Ah Im, Miguel Martín, Sherene Loi, Binghe Xu, Sara Hurvitz, Carlos Barrios, Michael Untch, Rebecca Moroose, Frances Visco, Federico Parnizari, Farhat Ghaznawi, Zheng Li, Sorcha Waters, Arunava Chakravartty, Dennis Slamon. Ribociclib (RIB) + nonsteroidal aromatase inhibitor (NSAI) as adjuvant treatment in patients with HR+/HER2− early breast cancer: final invasive disease–free survival (iDFS) analysis from the NATALEE trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-03.

Abstract PO4-27-07: A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2)

Abstract Background: Camizestrant is a next-generation oral selective estrogen receptor (ER) degrader and pure ER antagonist being investigated in early and advanced breast cancer (BC). In postmenopausal women with advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative BC and disease recurrence or progression on or after ≤1 endocrine therapy (ET) in the advanced setting, camizestrant significantly prolonged progression-free survival compared with fulvestrant in the Phase 2 SERENA-2 trial. Camizestrant may also provide benefit in the early BC setting. Following locoregional therapy (surgery ± radiotherapy), standard adjuvant treatment of ET with or without chemotherapy and/or a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has shown significant benefit in decreasing the risk of recurrence of stage I–III ER-positive/HER2-negative BC. However, BC recurrence as incurable metastatic disease is still common. Thus, adjuvant therapeutic options with improved clinical outcomes are needed. The CAMBRIA-2 study (NCT05952557) aims to assess whether upfront camizestrant can improve outcomes compared with standard ET as adjuvant treatment in patients with ER-positive/HER2-negative early BC with an intermediate-high or high risk of recurrence after definitive locoregional therapy. Trial design: This ongoing Phase 3, randomized, open-label study is enrolling women (pre-, peri-, or postmenopausal) and men with ER-positive/HER2-negative (HER2-negative status defined as immunohistochemistry 0, or 1+, or in situ hybridization-negative) early BC who are at intermediate-high or high risk of recurrence (as defined in the protocol) after having completed definitive locoregional therapy (surgery ± radiotherapy) ± (neo)adjuvant systemic chemotherapy, and who have no evidence of disease. Patients may have received up to 12 weeks of (neo)adjuvant ET prior to randomization. Patients are randomized (1:1) to receive camizestrant 75 mg ± abemaciclib ± luteinizing hormone-releasing hormone (LHRH) agonist or standard ET of the investigator’s choice (any aromatase inhibitor or tamoxifen) ± abemaciclib ± LHRH agonist for up to 7 years. The primary endpoint is invasive BC-free survival (IBCFS) (Standardized Definitions for Efficacy End Points [STEEP] 2.0 criteria). Secondary endpoints include invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) (STEEP 2.0 criteria), overall survival, safety, and health-related quality of life. Primary endpoint analysis will use a stratified log-rank test adjusting for stratification factors, assuming a two-sided significance level of 5%. Approximately 5500 patients will be randomized. Clinical trial identification: NCT05952557 Editorial acknowledgment: Writing assistance was provided by Clare Davis of BOLDSCIENCE Inc., funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca Funding: This study was supported by AstraZeneca. Citation Format: Sibylle Loibl, Yeon Park, Sara Tolaney, Ioanna Gioni, Simon Johnston, Teresa Klinowska, Ingrid A. Mayer, Raquel Nunes, Barbara Pistilli, Mary Stuart, Angela Quintana, Andrew Walding, Michael Gnant. A Phase 3, randomized, open-label study of upfront camizestrant vs standard endocrine therapy as adjuvant treatment for ER-positive/HER2-negative early breast cancer with intermediate-high or high risk of recurrence (CAMBRIA-2) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-27-07.

Abstract GS03-07: Protocol-defined biomarker analysis in the PALLAS (AFT-05) adjuvant trial: Genomic subtype derived from RNA sequencing of HR+/HER2- early breast cancer

Abstract Background. The phase 3 PALLAS trial (NCT02513394) compared two years of the CDK4/6 inhibitor palbociclib with endocrine therapy of provider choice, versus endocrine therapy alone, as adjuvant treatment for patients with Stage II-III hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer. Genomic subtype (PAM50 intrinsic subtype) measured from whole-transcriptome RNA sequencing data was defined in the protocol of the PALLAS trial as the primary biomarker for analysis of prediction and prognosis. Clinical data have been previously presented (Gnant et al, JCO 2022), and the trial now has 5-year median follow-up. Methods. As part of trial eligibility, all participants in PALLAS provided a tumor tissue block prior to randomization (surgical if primary resection, core biopsy if neoadjuvant treatment) for translational analyses (TRANS-PALLAS). The biorepository and laboratory were blinded to identity and processed samples in random order, to minimize bias. Nucleic acids were extracted from samples with sufficient tumor tissue and cellularity (&amp;gt;25 mm2 with ≥20% cancer nuclei). The Genome Sequencing Center at Washington University St. Louis performed whole-transcriptome RNA sequencing. Libraries were prepared from 1 µg DNase-1 treated total RNA, if total RNA DV200 &amp;gt;28 (Agilent Bioanalyzer), using an unbiased library protocol of RNA HyperPrep kit with RiboErase (HMR) (Kapa Biosystems, Wilmington, MA). 100 bp paired-end sequencing was performed on NovaSeq 6000 using S4 Reagent Kit (Illumina, San Diego, CA), with 48 libraries pooled per lane. Intrinsic subtype was determined using Bioclassifier package (Research PAM50 script, Parker et al.) only for the analysis population of primary breast cancer samples that had not been exposed to prior neoadjuvant therapy. Invasive disease-free survival (IDFS) will be visualized using Kaplan-Meier plots, with log-rank test between groups. Cox models of proportional hazards will be developed to evaluate prognosis adjusted for known clinical covariates, or for predictive interactions. The pre-defined level of significance is a two-sided 0.05. Results. From the total study population of 5796 enrolled patients, 4655 tissue blocks had sufficient tumor content to process for RNA, with 3931 yielding sufficient RNA for sequencing, and 2669/4655 (57.3%) submitted tissue blocks had DV200 ≥28 and were successfully sequenced. Clinical unblinding revealed 2370 unique patients (1182 in the palbociclib treatment arm and 1188 in the control arm) with intrinsic subtype defined from their untreated primary tumor: 1555 (65.6%) luminal A, 287 (12.1%) luminal B, 167 (7.0%) HER2-enriched, 310 (13.1%) basal-like, 51 (2.2%) normal-like. We will report the results for association of molecular subtype, proliferation score, and Risk of Recurrence (ROR) scores with invasive disease-free survival (IDFS) by treatment arm at the meeting. Conclusions. The TRANS-PALLAS cohort represents one of the largest biorepositories of HR+/HER2- early breast cancer reflecting contemporary systemic management in the framework of a prospectively randomized global trial. Required tumor block submission in this phase 3 trial yielded data from unbiased whole-transcriptome RNA sequencing of the primary tumor prior to treatment from 41% of the PALLAS participants. The proportion of luminal A cancers was unexpectedly high (66%), indicating a lower-risk distribution of cancers in this population. The planned analyses of prediction and prognosis are ongoing and those results will be presented at the time of the meeting. Support: AFT, ABCSG, Pfizer, ECOG-ACRIN, NSABP Foundation, GBG, BIG; Clinicaltrials.gov Identifier: NCT02513394; https://acknowledgments.alliancefound.org Citation Format: Daniel Stover, Dominik Hlauschek, Erica Mayer, W. Fraser Symmans, Mark Watson, Iros Barozzi, Martin Filipits, Karla Ballman, Meritxell Bellet- Ezquerra, Justin Balko, Gabor Rubovszky, Nicholas Zdenkowski, Adam Brufsky, Guenther Steger, Claudine Isaacs, Sibylle Loibl, Fernando Henao, Meredith Regan, Yuan Liu, Christian Fesl, Patrick O'Brien, Angela DeMichele, Michael Gnant, Otto Metzger. Protocol-defined biomarker analysis in the PALLAS (AFT-05) adjuvant trial: Genomic subtype derived from RNA sequencing of HR+/HER2- early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-07.

Autologous platelet-rich plasma as adjuvant treatment in patients with refractory endometrial growth: Preliminary results from a 2-year prospective study in a Spanish reference unit of assisted human reproduction

Autologous platelet-rich plasma as adjuvant treatment in patients with refractory endometrial growth: Preliminary results from a 2-year prospective study in a Spanish reference unit of assisted human reproduction

Discovering the Potential Value of Coenzyme Q10 as an Adjuvant Treatment in Patients With Depression.

Depressive disorder or mental cold is the most common mental disorder, and depression exists all over the world and in all countries and cultures. The results of several studies have shown that using compounds with antioxidant properties has been fruitful in patients with depression. Coenzyme Q10 (CoQ10) is a fat-soluble antioxidant and exerts its antioxidant effect by directly neutralizing free radicals or reducing tocopherol and preventing the inhibition of mitochondrial activity because of oxidative stress. This study aimed to investigate the effects of oral CoQ10 in patients with depression as an adjunctive treatment. Sixty-nine patients with moderate and severe depression were randomly divided into 2 CoQ10 groups (36) and placebo (33). The first group of patients received CoQ10 supplements at a dose of 200 mg daily for 8 weeks along with standard interventions and treatments for depression, and the second group received standard treatments for depression along with a placebo. The change in the score of Montgomery-Åsberg Depression Rating Scale depression scale was evaluated 4 and 8 weeks after the intervention. Also, at baseline and 8 weeks later at the end of the study, serum levels of total antioxidant capacity, total thiol groups, nitric oxide, malondialdehyde, and interleukin 6 were assessed. The changes in the depression score at the end of the study showed that, in the group receiving the CoQ10 supplement after 8 weeks, there was a reduction in depression symptoms, which was statistically significant compared with before the start of the study Meanwhile, no significant changes were observed in the patients of the placebo group in terms of symptom reduction. Compared with baseline and the placebo condition, serum levels of nitric oxide and total thiol groups significantly decreased and increased, respectively. Also, no statistically significant changes were observed for interleukin 6, malondialdehyde, and total antioxidant capacity. A dose of 200 mg of CoQ10 supplement daily for 8 weeks can reduce depression and fatigue, as well as improve the quality of life of patients with depression. In addition, CoQ10 can significantly improve inflammation and oxidative stress status in patients with depression.

Phase I dose escalation study for In Vivo Lung Perfusion (IVLP) as an adjuvant treatment for patients with resectable pulmonary metastasis of bone or soft tissue sarcomas

BackgroundMetastatic sarcoma is an aggressive disease with few effective treatment options. Standard of care for limited pulmonary metastasis is surgical resection, however micrometastasis are often present and go undetected. Here, we determine the maximal tolerated dose and safety of doxorubicin delivered via In Vivo Lung Perfusion (IVLP) for patients with resectable sarcoma pulmonary metastases. MethodsThis is a phase I dose escalation study using doxorubicin during IVLP in sarcoma patients with surgically resectable bilateral pulmonary metastases from 2017 to 2022. While the bilateral disease was surgically resected, only a single side underwent IVLP with doxorubicin at different dose levels (DL 1–3). Intraoperative serum, perfusate and lung tissue were collected and evaluated for doxorubicin levels. Patients were closely monitored intra- and post-operatively for adverse events. Results8 patients consented and six patients met the inclusion criteria, while 2 patients had progressive disease before surgery and were excluded. Initial dose of 5ucg/ml perfusate of doxorubicin (DL1) was used in 1 patient, 3 patients had a dose escalation to 7ucg/ml (DL2), 2 patients with the final dose escalation of doxorubicin to 9ucg/ml (DL3). With DL3, lung infiltrates were observed, therefore it was declared as the maximal administered dose and DL2 was deemed to be the recommended phase 2 dose (RP2D). There were no safety concerns during the IVLP procedure and no deaths within the first 90 days. ConclusionsHere, we demonstrate the safety and feasibility of doxorubicin as a treatment during IVLP for resectable limited pulmonary metastases for sarcomas.

Abstract CT107: Durable immunogenicity of ELI-002 2P in AMPLIFY-201: Lymph node targeted mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer

Abstract Background: Colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC) are the second and third leading causes of cancer death in the United States. Kirsten rat sarcoma driver mutations (mKRAS) are prevalent in CRC (52%) and PDAC (93%), making them attractive targets for immunotherapy where therapeutic options are otherwise limited. ELI-002 2P immunotherapy enhances lymph node delivery and immune responses using Amphiphile (Amph) modification of vaccine components. 84% of patients (21/25) induced mKRAS-specific T-cells post-vaccination as assessed by direct ex vivo Fluorospot and/or ICS assays with an average 58-fold increase from baseline. A balanced CD4+ and CD8+ T cell response was observed in 59% of patients. Reductions in ctDNA or serum tumor biomarker antigen from baseline were observed in 84% of patients (21/25) and 24% (6/25) had complete biomarker clearance. The induction of strong mKRAS T cell responses correlated with reductions in tumor biomarker response/clearance and relapse-free survival (RFS) in patients. Methods: ELI-002-001 is a first-in-human Phase 1 trial (NCT04853017) of ELI-002 2P cancer vaccine as adjuvant treatment for patients with high relapse-risk mKRAS+ PDAC and CRC. ELI-002 2P consists of 2 Amph-modified mKRAS peptide antigens, Amph-G12D and Amph-G12R (Amph-Peptides 2P), and an Amph-modified immune-stimulatory oligonucleotide adjuvant (Amph-CpG-7909). 25 patients received ELI-002 2P at 1.4 mg of Amph-Peptides 2P and Amph-CpG-7909 at 5 dose levels; 0.1, 0.5, 2.5, 5, and 10 mg. Peripheral blood and circulating tumor DNA (ctDNA) or serum tumor antigen were collected longitudinally to assess T cell immunogenicity and reductions in clinical biomarkers. Results: A majority of patients who received the booster immunizations maintained or increased mKRAS-specific T cell responses relative to baseline. A high frequency of polyfunctional cells secreting IFNγ, TNFα, IL-2, and/or Granzyme B was observed. CD4+ T regulatory cells were not induced after ELI-002 2P immunization. Assessment of the breadth of responses to 7 different KRAS mutations revealed broad cross-reactivity to KRAS mutants, including non-immunizing epitopes, and no responses to WT. Additional phenotypic and functional qualities were assessed. Conclusions: ELI-002 is an off-the-shelf vaccine targeting common KRAS tumor mutations demonstrating several key advantages: lymph node-targeted vaccine design, high immunogenicity, with balanced CD4+ and CD8+ T cell responses, HLA-agnostic activity, and targeting of vaccine antigens critical for tumor survival. A randomized Phase 2 clinical trial (NCT05726864) investigating a 7-peptide formulation (G12D, R, V, A, C, S, G13D) is underway. Citation Format: James R. Perry, Haley VanWyk, Amy M. Tavares, Thian Kheoh, Esther Welkowsky, Christopher M. Haqq, Peter C. DeMuth, Lisa K. McNeil. Durable immunogenicity of ELI-002 2P in AMPLIFY-201: Lymph node targeted mKRAS-specific amphiphile vaccine in pancreatic and colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT107.

Exploring sedentary behavior during neo- or adjuvant treatment in patients with cancer: A phenomenological study

PurposeIncreased sedentary behavior during cancer treatment is common, which may have negative long-term health effects. Understanding patients' experience of sedentary behavior during neo- or adjuvant cancer treatment may be crucial in developing effective support for patients to reduce sedentary behavior. Therefore, the present study aimed to explore sedentary behavior in patients undergoing neo- or adjuvant cancer treatment. MethodsEleven interviews were conducted with patients undergoing treatment for breast, prostate, and colorectal cancer. Participants were recruited from a university hospital in Sweden. Interviews were analyzed phenomenologically, and the results were presented as descriptions of the phenomenon sedentary behavior. ResultsThe overarching theme of sedentary behavior during cancer treatment was that sedentary behavior is experienced through being physically active or not. Furthermore, experiences of sedentary behavior increased with side effects and varied depending on the type and phase of cancer treatment, meaning that sedentary behavior is an adjustment to side effects. Additionally, sedentary behavior was influenced by life circumstances and social interaction, such as work status and having social support. Finally, sedentary behavior is influenced by strategies and motivations, such as the perceived benefits of physical activity and self-image. ConclusionsSedentary behavior is difficult for patients to discern, which is why health care personnel may need to help patients by increasing awareness of the negative impact of sedentary behavior in a way that does not stigmatize patients. Furthermore, developing support that targets periods with more side effects and helping patients reduce sedentary behavior throughout changing life circumstances may be helpful.

Development and validation of a novel model to predict recurrence-free survival and melanoma-specific survival after sentinel lymph node biopsy in patients with melanoma: an international, retrospective, multicentre analysis

The introduction of adjuvant systemic treatment for patients with high-risk melanomas necessitates accurate staging of disease. However, inconsistencies in outcomes exist between disease stages as defined by the American Joint Committee on Cancer (8th edition). We aimed to develop a tool to predict patient-specific outcomes in people with melanoma rather than grouping patients according to disease stage. Patients older than 13 years with confirmed primary melanoma who underwent sentinel lymph node biopsy (SLNB) between Oct 29, 1997, and Nov 11, 2013, at four European melanoma centres (based in Berlin, Germany; Amsterdam and Rotterdam, the Netherlands; and Warsaw, Poland) were included in the development cohort. Potential predictors of recurrence-free and melanoma-specific survival assessed were sex, age, presence of ulceration, primary tumour location, histological subtype, Breslow thickness, sentinel node status, number of sentinel nodes removed, maximum diameter of the largest sentinel node metastasis, and Dewar classification. A prognostic model and nomogram were developed to predict 5-year recurrence-free survival on a continuous scale in patients with stage pT1b or higher melanomas. This model was also calibrated to predict melanoma-specific survival. Model performance was assessed by discrimination (area under the time-dependent receiver operating characteristics curve [AUC]) and calibration. External validation was done in a cohort of patients with primary melanomas who underwent SLNB between Jan 30, 1997, and Dec 12, 2013, at the Melanoma Institute Australia (Sydney, NSW, Australia). The development cohort consisted of 4071 patients, of whom 2075 (51%) were female and 1996 (49%) were male. 889 (22%) had sentinel node-positive disease and 3182 (78%) had sentinel node-negative disease. The validation cohort comprised 4822 patients, of whom 1965 (41%) were female and 2857 (59%) were male. 891 (18%) had sentinel node-positive disease and 3931 (82%) had sentinel node-negative disease. Median follow-up was 4·8 years (IQR 2·3-7·8) in the development cohort and 5·0 years (2·2-8·9) in the validation cohort. In the development cohort, 5-year recurrence-free survival was 73·5% (95% CI 72·0-75·1) and 5-year melanoma-specific survival was 86·5% (85·3-87·8). In the validation cohort, the corresponding estimates were 66·1% (64·6-67·7) and 83·3% (82·0-84·6), respectively. The final model contained six prognostic factors: sentinel node status, Breslow thickness, presence of ulceration, age at SLNB, primary tumour location, and maximum diameter of the largest sentinel node metastasis. In the development cohort, for the model's prediction of recurrence-free survival, the AUC was 0·80 (95% CI 0·78-0·81); for prediction of melanoma-specific survival, the AUC was 0·81 (0·79-0·84). External validation showed good calibration for both outcomes, with AUCs of 0·73 (0·71-0·75) and 0·76 (0·74-0·78), respectively. Our prediction model and nomogram accurately predicted patient-specific risk probabilities for 5-year recurrence-free and melanoma-specific survival. These tools could have important implications for clinical decision making when considering adjuvant treatments in patients with high-risk melanomas. Erasmus Medical Centre Cancer Institute.

Evaluation of post-operative complications and adjuvant treatments following immediate prepectoral versus subpectoral direct-to-implant breast reconstruction without acellular dermal matrix

BackgroundIn immediate breast reconstruction (IBR), it is unclear whether there is any difference in the complication rates between prepectoral versus subpectoral implant placement without acellular dermal matrix (ADM). AimTo compare the rates of early post-operative complications and time to initiation of adjuvant treatment in patients undergoing IBR between prepectoral and subpectoral implant placement without ADM for the two surgical procedure. MethodsWe retrospectively retrieved data of patients who underwent IBR with prepectoral versus subpectoral implant placement between January 1, 2020 and December 31, 2022 in a large cancer center in France. ResultsWe included 192 patients: 119 in the prepectoral and 73 in the subpectoral group. Their clinical characteristics were similar. Thirty patients (15.6%) received adjuvant chemotherapy, among them 27 (14.1%) received it within 12 weeks, and there was no difference between the groups (p = 0.12). In the prepectoral group, 39 patients (32.8%) received adjuvant radiotherapy versus 5 (6.8%) in the subpectoral group (p < 0.001), but there was no significant difference in time to treatment commencement. Overall, 35 patients (29.4%) in the prepectoral group and 17 (23.3%) in the subpectoral group experienced post-operative complications (p = 0.44). Using multivariable analysis, the only factor associated with post-operative complications was determined to be mastectomy weight (odds ratio 1.98 (1.10–3.59) for weight ≥500 g; p = 0.02). ConclusionPrepectoral implant placement without ADM can be proposed to patients undergoing IBR with an indication for adjuvant treatment. However, in our study, the reoperation rate with this technique was slightly higher (p = 0.008). This is partly due to the learning curve for surgeons using this new technique.

The Effectiveness of Adjuvant PD-1 Inhibitors in Patients With Surgically Resected Stage III/IV Acral Melanoma.

Our aim was to assess the efficacy of adjuvant programmed cell death protein-1 (PD-1) inhibitors and compare the other adjuvant treatments in patients with surgically resected stage III or IV acral melanoma. This study is a multicenter, retrospective analysis. We included 114 patients with stage III or IV acral malignant melanoma who underwent surgery within the past 10 years. We analyzed the effect of adjuvant programmed cell death protein-1 inhibitors on disease-free survival (DFS). The mean follow-up was 40 months, during which 69 (59.5%) patients experienced recurrence. Among the participants, 64 (56.1%) received systemic adjuvant therapy. Specifically, 48.4% received anti-PD-1 therapy, 29.7% received interferon, 14.1% received tezozolomide, and 7.8% received B-Raf proto-oncogene/mitogen-activated protein kinase inhibitors. Patients who received adjuvant therapy had a median DFS of 24 (10.9-37.2) months, whereas those who did not receive adjuvant therapy had a median DFS of 15 (9.8-20.2) months. Multivariate analysis for DFS revealed that the receipt of adjuvant therapy and lymph node metastasis stage were independent significant parameters ( P = 0.021, P = 0.018, respectively). No statistically significant difference was observed for DFS between programmed cell death protein-1 inhibitor treatment and other adjuvant treatments. Regarding overall survival (OS), patients who received adjuvant treatment had a median OS of 71 (30.4-111.7) months, whereas those who did not receive adjuvant treatment had a median OS of 38 (16.7-59.3; P = 0.023) months. In addition, there were no significant differences in OS observed between various adjuvant treatment agents ( P = 0.122). In our study, we have shown that adjuvant therapy had a positive effect on both DFS and OS in patients with stages III-IV acral melanoma who underwent curative intent surgery. Notably, we found no significant differences between anti-PD-1 therapy and other adjuvant therapies.

Low-Volume Metastases in Cervical Cancer: Does Size Matter?

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer, and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. Part of the undisputed value of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make reaching any conclusions on this topic hard. Current guidelines suggest considering micrometastases (MIC) as a node-positive disease, while considering isolated tumor cells (ITC) as a node-negative disease with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, and prognostic and therapeutic roles of LVM and to underline the present and future challenges we are facing. We hope that this review will guide further research, giving robust evidence on LVM and their impacts on clinical practice.

Systematic review with expert consensus on use of extracorporeal hemoadsorption in septic shock: An Indian perspective.

Septic shock is a severe form of sepsis characterised by deterioration in circulatory and cellular-metabolic parameters. Despite standard therapy, the outcomes are poor. Newer adjuvant therapy, such as CytoSorb® extracorporeal haemoadsorption device, has been investigated and shown promising outcome. However, there is a lack of some guidance to make clinical decisions on the use of CytoSorb® haemoadsorption as an adjuvant therapy in septic shock in Indian Setting. Therefore, this expert consensus was formulated. To formulate/establish specific consensus statements on the use of CytoSorb® haemoadsorption treatment based on the best available evidence and contextualised to the Indian scenario. We performed a comprehensive literature on CytoSorb® haemoadsorption in sepsis, septic shock in PubMed selecting papers published between January 2011 and March 2023 2021 in English language. The statements for a consensus document were developed based on the summarised literature analysis and identification of knowledge gaps. Using a modified Delphi approach combining evidence appraisal and expert opinion, the following topics related to CytoSorb® in septic shock were addressed: need for adjuvant therapy, initiation timeline, need for Interleukin -6 levels, duration of therapy, change of adsorbers, safety, prerequisite condition, efficacy endpoints and management flowchart. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. Eleven expert members from critical care, emergency medicine, and the intensive care participated and voted on nine statements and one open-ended question. All 11 experts in the consensus group (100%) participated in the first, second and third round of voting. After three iterative voting rounds and adapting two statements, consensus was achieved on nine statements out of nine statements. The consensus expert panel also recognised the necessity to form an association or society that can keep a registry regarding the use of CytoSorb® for all indications in the open-ended question (Q10) focusing on "future recommendations for CytoSorb® therapy". This Indian perspective consensus statement supports and provides guidance on the use of CytoSorb® haemoadsorption as an adjuvant treatment in patients with septic shock to achieve optimal outcomes.

128 (PB-128) Poster - Impact of Oncotype DX Recurrence Score and Nottingham Prognostic Index on adjuvant treatment in patients with axillary lymph node micrometastasis in early breast cancer

128 (PB-128) Poster - Impact of Oncotype DX Recurrence Score and Nottingham Prognostic Index on adjuvant treatment in patients with axillary lymph node micrometastasis in early breast cancer

Evaluation of purine-nucleoside degrading ability and in vivo uric acid lowering of Streptococcus thermophilus IDCC 2201, a novel antiuricemia strain.

This study evaluated 15 lactic acid bacteria with a focus on their ability to degrade inosine and hypo-xanthine-which are the intermediates in purine metabolism-for the management of hyperuricemia and gout. After a preliminary screening based on HPLC, Lactiplantibacillus plantarum CR1 and Lactiplantibacillus pentosus GZ1 were found to have the highest nucleoside degrading rates, and they were therefore selected for further characterization. S. thermophilus IDCC 2201, which possessed the hpt gene encoding hypoxanthine-guanine phosphoribosyltransferase (HGPRT) and exhibited purine degradation, was also selected for further characterization. These three selected strains were examined in terms of their probiotic effect on lowering serum uric acid in a Sprague-Dawley (SD) rat model of potassium oxonate (PO)-induced hyperuricemia. Among these three strains, the level of serum uric acid was most reduced by S. thermophilus IDCC 2201 (p < 0.05). Further, analysis of the microbiome showed that administration of S. thermophlilus IDCC 2201 led to a significant difference in gut microbiota composition compared to that in the group administered with PO-induced hyperuricemia. Moreover, intestinal short-chain fatty acids (SCFAs) were found to be significantly increased. Altogether, the results of this work indicate that S. thermophilus IDCC 2201 lowers uric acid levels by degrading purine-nucleosides and also restores intestinal flora and SCFAs, ultimately suggesting that S. thermophilus IDCC 2201 is a promising candidate for use as an adjuvant treatment in patients with hyperuricemia.

Enhancing outcomes: neurosurgical resection in brain metastasis patients with poor Karnofsky performance score - a comprehensive survival analysis.

A reduced Karnofsky performance score (KPS) often leads to the discontinuation of surgical and adjuvant therapy, owing to a lack of evidence of survival and quality of life benefits. This study aimed to examine the clinical and treatment outcomes of patients with KPS < 70 after neurosurgical resection and identify prognostic factors associated with better survival. Patients with a preoperative KPS < 70 who underwent surgical resection for newly diagnosed brain metastases (BM) between 2007 and 2020 were retrospectively analyzed. The KPS, age, sex, tumor localization, cumulative tumor volume, number of lesions, extent of resection, prognostic assessment scores, adjuvant radiotherapy and systemic therapy, and presence of disease progression were analyzed. Univariate and multivariate logistic regression analyses were performed to determine the factors associated with better survival. Survival > 3 months was considered favorable and ≤ 3 months as poor. A total of 140 patients were identified. Median overall survival was 5.6 months (range 0-58). There was no difference in the preoperative KPS between the groups of > 3 and ≤ 3 months (50; range, 20-60 vs. 50; range, 10-60, p = 0.077). There was a significant improvement in KPS after surgery in patients with a preoperative KPS of 20% (20 vs 40 ± 20, p = 0.048). In the other groups, no significant changes in KPS were observed. Adjuvant radiotherapy was associated with better survival (44 [84.6%] vs. 32 [36.4%]; hazard ratio [HR], 0.0363; confidence interval [CI], 0.197-0.670, p = 0.00199). Adjuvant chemotherapy and immunotherapy resulted in prolonged survival (24 [46.2%] vs. 12 [13.6%]; HR 0.474, CI 0.263-0.854, p = 0.013]. Systemic disease progression was associated with poor survival (36 [50%] vs. 71 [80.7%]; HR 5.975, CI 2.610-13.677, p < 0.001]. Neurosurgical resection is an appropriate treatment modality for patients with low KPS. Surgery may improve functional status and facilitate further tumor-specific treatment. Combined treatment with adjuvant radiotherapy and systemic therapy was associated with improved survival in this cohort of patients. Systemic tumor progression has been identified as an independent factor for a poor prognosis. There is almost no information regarding surgical and adjuvant treatment in patients with low KPS. Our paper provides novel data on clinical outcome and survival analysis of patients with BM who underwent surgical treatment.

Anticancer effect of zoledronic acid in endocrine-resistant breast cancer cells via HER-2 signaling

HER-2 overexpression is a major mechanism involved in endocrine-resistant breast cancer, which has very limited treatment options. Zoledronic acid (ZA) is a drug in the bisphosphonate group used to treat osteoporosis. ZA was reported to exhibit activity in various cancers, with higher efficacy associated with estrogen-deprivation states. ZA inhibits cell proliferation in lung cancer through the epidermal growth factor receptor signaling pathway. Because endocrine-resistant breast cancer cells overexpress HER-2 and grow independently without estrogen, ZA may exert anticancer effects in these cell types. The inhibitory effects and mechanisms of ZA in endocrine-resistant cells through HER-2 signaling were investigated. The efficacy of ZA was higher in the endocrine-resistant breast cancer cells when compared with the wild-type cells. ZA also exhibited a synergistic effect with fulvestrant and may circumvent fulvestrant resistance. ZA decreased phosphorylated ERK (pERK) levels in resistant cell lines and attenuated HER-2 signaling in tamoxifen- and fulvestrant-resistant cells. ZA significantly decreased HER-2 levels and its downstream signaling molecules, including pAKT and pNF-κB in fulvestrant-resistant breast cancer cells. This inhibitory effect may explain the lower IC50 values of ZA in fulvestrant-resistant cells compared with tamoxifen-resistant cells. Moreover, ZA inhibited the migration and invasion in the resistant cell lines, suggesting an ability to inhibit tumor metastasis. The results indicate that ZA has potential for repurposing as an adjuvant treatment for patients with endocrine-resistant breast cancer.